Endoplasmic reticulum stress-regulated high temperature requirement A1 (HTRA1) modulates invasion and angiogenesis-related genes in human trophoblasts
Endoplasmic reticulum stress-regulated high temperature requirement A1 (HTRA1) modulates invasion and angiogenesis-related genes in human trophoblasts
复制标题
内质网应激调节高温需求 A1 (HTRA1) 调节人滋养层细胞侵袭和血管生成相关基因
DOI：
10.1016/j.jphs.2022.10.003
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发表时间：
2022
影响因子：
3.5
通讯作者：
Kiyoko Kato,Kazuhiro Tamura
中科院分区：
文献类型：
--
作者：
Kanoko Yoshida;Kazuya Kusama;Mana Azumi;Mikihiro Yoshie;Kiyoko Kato,Kazuhiro Tamura
妊娠期高血压疾病（HDP）影响约10%的孕妇，其发病机制仍不完全清楚。我们之前的研究表明，内质网（ER）应激影响高温需求A丝氨酸肽酶1 （HTRA1）的表达和滋养细胞的侵袭。然而，内质网应激参与HTRA亚型表达的调节和HDP的病理生理尚未在上皮外滋养细胞（EVTs）中得到表征。为了研究这一点，我们用内质网应激诱导剂thapsigarin （Thap）或Tunicamycin （Tuni）处理HTR8/SVneo EVTs细胞系。Thap或Tuni均可抑制滋养细胞侵袭，降低HTRA1和HTRA3的表达，但未改变HTRA2和HTRA4的表达。敲低HTRA1或HTRA3也能抑制滋养细胞的侵袭。此外，ER应激诱导剂或HTRA1沉默处理均增加了可溶性类膜酪氨酸激酶-1/胎盘生长因子（sFLT1/PlGF）的比率，这是HDP的一个标志。免疫组化分析显示HTRA1定位于HDP患者胎盘的evt和子宫内膜蜕膜。这些结果表明，内质网应激的因素可能通过HTRA1抑制evt的侵袭。
The pathogenesis of hypertensive disorder of pregnancy (HDP), which affects about 10% of pregnant women, is still incompletely understood. Our previous study showed that endoplasmic reticulum (ER) stress influences high-temperature requirement A serine peptidase 1 (HTRA1) expression and trophoblast invasion. However, the involvement of ER stress in the regulation of HTRA subtype expression and pathophysiology of HDP has not been characterized in extravillous trophoblasts (EVTs). To investigate this, HTR8/SVneo EVTs cell line was treated with the ER stress inducers Thapsigargin (Thap) or Tunicamycin (Tuni). Treatment with either Thap or Tuni inhibited trophoblast invasion, reduced HTRA1 and HTRA3 expression, but did not alter HTRA2 or HTRA4 expression. Knockdown of HTRA1 or HTRA3 also inhibited trophoblast invasion. Furthermore, treatment with either ER stress inducer or HTRA1 silencing increased the ratio of soluble fms-like tyrosine kinase-1/placental growth factor (sFLT1/PlGF), which is a marker of HDP. Immunohistochemical analysis revealed that HTRA1 is localized to EVTs and the endometrial decidua in the placenta of patients with HDP. These results suggest that factors that cause ER stress could result in the inhibition of EVTs invasion via HTRA1.